1. Field of the Invention
The present invention relates generally to a sustained-release formulation for once-daily oral administration containing Mosapride with a total weight of 200 mg or less.
2. Description of the Related Art
As is well known in the art, 4-amino-5-chloro-2-ethoxy-N-{[4-(4-fluorobenzyl)-2-morpholinyl]methyl}benzamide (Mosapride) is a compound having a structure represented by Chemical Formula 1 below. Mosapride and its physiologically acceptable salts are selective serotonin 5-hydroxytryptamine 4 (hereinafter, ‘5-HT4’) receptor agonists which selectively promote only the serotonin 5-HT4 receptors present in Plexus entercus, thus facilitating acetylcholine release from the nerve endings and also facilitating the movement of the digestive tract by constricting the smooth muscle of the digestive tract by the released acetylcholine, and thus serving as an effective drug for treating diabetic gastropathy, dyspepsia, gastritis, and gastroesophageal reflux disease. Mosapride is a safe drug free of the risks of arrhythmia and sudden cardiac death occurring in cisapride due to extension of QT intervals, dopamine-2 (D-2) receptor antagonistic action, central nervous system (CNS) adverse effects (extrapyramidal symptoms), and hyperprolactinemia (lactation, gynecomastia).

Mosapride, when orally administered, can be more than 93% absorbed in the digestive tract. Mosapride is distributed in the liver, small intestine, kidney, and adrenal glands at a concentration at least 10 times higher than that in blood plasma, distributed at high concentrations in the lungs, submaxillary gland, pancreas, hypophysis, thyroid gland, spleen, etc., and at a low concentration in eyeballs at about half the concentration in blood. Mosapride exhibits a fast drug effect by reaching its highest concentration in blood within from 0.5 hour to 1.4 hour when administered orally.
Due to the short half-life of Mosapride in the range of from 1.3 to 2 hours, Mosapride rapidly disappears once it is absorbed into a body, and thus it should be administered a few times because of its short duration of drug effect. Mosapride has been developed in tablets and is currently available on the market. Tablets containing 5 mg of Mosapride are recommended to be taken three times daily. Accordingly, it is necessary to improve the compliance of patients with the recommended use by reducing the number of administrations required, and also to maintain the drug effect by maintaining its concentration in blood.
Conventional sustained-release tablets have a disadvantage in that they require a long time for the drugs to reach an effective concentration in blood at the initial stage. Additionally, a fast exhibition of pharmacological activities of a given drug after its oral administration makes it difficult to maintain the effective pharmacological activities of the drug for 24 hours.